Previous work done in our laboratories has resulted in the establishment of physical models for the dissolution of hydroxyapatite and tooth enamel. These models have been used to quantitate the influences of solution composition (in terms of pH, buffer capacity, levels of calcium and phosphate, levels of foreign ions such as fluoride and strontium, and levels of other foreign agents such as dodecylamine) on dissolution kinetics of crystallite suspensions. A model has also been developed to correlate the suspension kinetics with the more complex situation of dissolution from a compressed pellet of hydroxyapatite. This model, valid for explaining initial dissolution rates at steady-state solution conditions indicates all the known situations in which subsurface dissolution as well as surface dissolution can occur, and predicts quite well the pattern of mineral density loss in the very early initial stages of demineralization. The goals of the proposed research are to extend the range of the current models. These models will encompass a wider variety of solution conditions at the crystal level, especially conditions that result in the transient formation of apatitic solid phases partially substituted with foreign ions such as fluoride. At the pellet level, the new models will account for the nonsteady-state response of the pellet to solution conditions, including such factors as local changes in density, porosity, and composition. A prerequisite for this extended pellet model is the more comprehensive crystal level model cited above. These models will enable us to make more mechanistic assessments of the development of carious lesions, including the effects of mineral carbonate and/or solution fluoride. In addition, planned experiments with additives such as alkylamines should lead to a much more detailed understanding of their action than is now possible.